A number of diseases are caused by disorders in cellular metabolism. For many of these diseases the nature of the metabolic defect has been identified, and the rapid progress of biomedical research continues to further our understanding of the precise mechanisms involved. For example, Type I diabetes is known to result from defective glucose metabolism associated with decreased levels of insulin, whereas different cancers are due to defective control of cellular division and proliferation associated with mutations in a variety of cellular genes, many of which have been identified. Many disorders in cellular metabolism are caused by somatic or hereditary genetic mutations which result either in inappropriate expression of a given gene product or expression of a defective gene product. However, environmental assaults such as chemical poisoning, physical damage or biological infection can also result in specific defects in cellular metabolism. In addition, cellular aging often results in metabolic disorders. Understanding the nature of a given metabolic disorder identifies targets/goals for an effective treatment.
A traditional approach to treatment consists of administering systemically, to a patient, a pharmaceutical compound or drug that overcomes the metabolic disorder. For example, administering exogenous insulin to a patient alleviates the symptoms of Type I diabetes. There are, however, several drawbacks to this type of drug therapy. For a pharmaceutical compound to be effective, it must be administered so that it reaches its site of action at an appropriate concentration. If the compound is provided systemically, whether administered orally or by injection, undesirable side effects may be caused by the systemic levels of the compound required for it to be effective at its site of action. This is the case for many chemotherapeutic agents used to treat various forms of cancer. Current attempts to overcome this problem consist of trying to target pharmaceutical compounds to their desired site of action for sustained periods of time at effective concentrations. There is not yet a reliable and general method for such targeted drug delivery.
An additional problem with traditional drug administration is that the drug must be stable and transportable to its site of action. For many diseases, the most appropriate therapeutic compound would be a specific protein, especially if the disease results from the absence of a functional form of that protein. However, delivering any given protein to its desired site of action can be complicated by its susceptibility to denaturation and proteolytic degradation, and by poor mobility to its desired site of action.
An alternative approach is gene therapy which attempts to overcome these problems by circumventing the requirement of transporting a protein to its site of action. The goal of gene therapy is to provide DNA encoding the desired protein to the site of action. The DNA then is transcribed and translated to produce the protein in therapeutically effective concentrations at the appropriate site in the body. However, gene therapy also faces a delivery problem of how to get the DNA to the appropriate cells. Current approaches to solving this problem consist of using viral vectors, liposome encapsulation, direct injection, or complexation with carrier proteins. At present, none of these approaches provides an effective and general method for getting DNA to any desired site of action within the body. Current gene therapy technology also does not address the required duration of therapy. Hereditary diseases, for example, might require constant therapy to correct the inherited metabolic disorder. On the other hand, cancer treatment may only be needed for a time sufficient to destroy the cancer cells.
There is, therefore, a need in the art for effective devices and methods for delivering physiologically useful compounds to any desired site of action, in a controlled fashion. It is an object of the present invention to provide such devices and methods.